POS1522 CHANGES IN SERUM CYTOKINES BY WEEK 24 CORRELATE WITH LONG-TERM EFFICACY OF GUSELKUMAB THROUGH 2-YEARS IN BIO-NAÏVE ADULTS WITH PSA
Authors: S. Siebert, G. Schett, S. P. Raychaudhuri, M. Guma, W. Chen, S. Gao, S. D. Chakravarty, M. Shawi, P. Rahman
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The IL-23p19 inhibitor guselkumab (GUS) has shown robust efficacy vs placebo (PBO) in phase 3 DISCOVER-1 and -2 studies of adults with active psoriatic arthritis (PsA) <sup>[1,2]</sup>, with continuous overall clinical improvement observed through 2 years of DISCOVER-2 <sup>[3]</sup>. GUS has previously been shown to significantly reduce levels of inflammatory biomarkers associated with PsA over 24 weeks <sup>[4]</sup>. <h3>Objectives</h3> To assess whether earlier changes (by Week [W] 24) in serum biomarker levels associate with long-term (W100) clinical response to GUS. <h3>Methods</h3> DISCOVER-2 enrolled biologic-naïve adults with active PsA ≥6 months defined by the CASPAR criteria, swollen and tender joint counts ≥5, and C-reactive protein (CRP) ≥0.6 mg/dL. Patients (pts) were randomized 1:1:1 to GUS 100mg at W0, W4, then every 4 weeks (Q4W); GUS at W0, W4, then Q8W; or PBO <sup>[2]</sup>. Using Spearman linear regression and General linear model, serum cytokine levels determined in GUS-treated pts (pooled Q4W/Q8W) were assessed for: 1) correlations between reductions in cytokine levels, including selected Th17 cytokines (IL-17A, IL-17F, IL-22), acute phase cytokines (CRP, serum amyloid protein A [SAA], IL-6), and β-defensin 2 (BD-2), from baseline (BL) at W24 and in PsA disease severity from BL at W100, measured by changes in Disease Activity in PSoriatic Arthritis (DAPSA) scores, Psoriatic Arthritis Disease Activity Score (PASDAS), and Psoriasis Area and Severity Index (PASI) scores (significant correlation=r&gt;0.25 and p&lt;0.05); and 2) associations between changes in selected cytokine levels from BL through W24 and achievement of ACR50 response at W100. <h3>Results</h3> BL demographics, disease severity, and medication use of GUS-treated DISCOVER-2 pts with available biomarker data (N=100) were consistent with the overall GUS-treated DISCOVER-2 population (N=493). With GUS treatment, PASI score change from BL at W100 correlated with changes from BL at W24 in serum BD-2, IL-17A, IL-17F, and IL-22 levels (all r&gt;0.25, p&lt;0.05; <b>Table 1</b>), though PASDAS and DAPSA score change at W100 did not correlate with changes in these biomarkers at W24. DAPSA score change at W100 correlated with changes at W24 in serum IL-6. W100 ACR50 responders (N=53) to GUS also demonstrated significantly lower serum CRP, SAA, and IL-6 levels at W24 than nonresponders (N=39) (p&lt;0.05; <b>Figure 1</b>). <h3>Conclusion</h3> This analysis reported correlations between earlier changes in Th17 cytokine levels and long-term reductions in PASI scores, and associations between earlier changes in acute phase cytokine levels and long-term ACR50 response with GUS. The substantial reductions in these cytokines from BL at W24 may portend durable improvements in skin and joint symptoms of PsA. <h3>References</h3> [1]Deodhar A, et al. <i>Lancet</i> 2020;395:1115-25 [2]Mease P, et al. <i>Lancet</i> 2020;395:1126-36 [3]McInnes IB, et al. <i>Arthritis Rheumatol</i> 2022;74(3):475-85 [4]Sweet K, et al. <i>RMD Open</i> 2021;7:e001679 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Stefan Siebert Speakers bureau: AbbVie, GSK, Janssen, UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, UCB, Grant/research support from: AbbVie, Amgen (previously Celgene), Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Janssen, UCB, Georg Schett Speakers bureau: Amgen, AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis and UCB, Siba P Raychaudhuri Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Monica Guma Consultant of: Novartis, Pfizer, Gilead, Genentech, and Sonoma Biotherapeutics, Grant/research support from: Novartis, Pfizer, Gilead, Genentech, and Sonoma Biotherapeutics, Warner Chen Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Sheng Gao Shareholder of: Johnson &amp; Johnson, of which Janssen Research &amp; Development is a wholly owned subsidiary, Employee of: Janssen Research &amp; Development, LLC, Soumya D Chakravarty Shareholder of: Johnson &amp; Johnson, of which Janssen Scientific Affairs LLC is a wholly owned subsidiary, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis.